Ovine fetal adaptations to chronically reduced  urine flow: preservation of amniotic fluid volume

Mann, Stephanie E., Mark J. M. Nijland, and Michael G. Ross.Ovine fetal adaptations to chronically reduced urine flow: preservation of amniotic fluid volume. J. Appl. Physiol. 81(6): 2588–2594, 1996.—Adequate amniotic fluid (AF) volume is maintained by a balance of fetal fluid production (lung liquid and urine) and resorption (swallowing and intramembranous flow). Because fetal urine is the principle source of AF, alterations in urine flow and composition directly impact AF dynamics. Intra-amniotic 1-desamino-8-d-arginine vasopressin (DDAVP) is rapidly absorbed into fetal plasma and induces a marked fetal urinary antidiuresis. To examine the effect of intra-amniotic- DDAVP-induced fetal urinary responses on AF volume and composition, six chronically prepared ewes with singleton fetuses (gestation 128 ± 2 days) were studied for 72 h after a single intra-amniotic DDAVP (50-μg) injection. After DDAVP, fetal urine osmolality significantly increased at 2 h (157 ± 13 to 253 ± 21 mosmol/kg) and remained elevated at 72 h (400 ± 13 mosmol/kg). Urinary sodium (33.0 ± 4.5 to 117.2 ± 9.7 meq/l) and chloride (26.0 ± 2.8 to 92.4 ± 8.1 meq/l) concentrations similarly increased. AF osmolality increased (285 ± 3 to 299 ± 4 mosmol/kgH2O), although there was no change in fetal plasma osmolality (294 ± 2 mosmol/kg). Despite a 50% reduction in fetal urine flow (0.12 ± 0.03 to 0.05 ± 0.02 ml ⋅ kg−1 ⋅ min−1at 2 h and 0.06 ± 0.01 ml ⋅ kg−1 ⋅ min−1after 72 h), AF volume did not change (693 ± 226 to 679 ± 214 ml). There were no changes in fetal arterial blood pressures, pH,[Formula: see text], or[Formula: see text] after DDAVP. We conclude the following. 1) Intra-amniotic DDAVP injection induces a prolonged decrease in fetal urine flow and increases in urine and AF osmolalities. 2) Despite decreased urine flow, AF volume does not change. We speculate that, in response to DDAVP-induced fetal oliguria, reversed intramembranous flow (from isotonic fetal plasma to hypertonic AF) preserves AF volume.

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Maternal DDAVP-induced hyponatremia preserves fetal urine flow during acute fetal hemorrhage

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00765.2002 ◽

2003 ◽

Vol 285 (2) ◽

pp. R373-R379 ◽

Cited By ~ 1

Author(s):

Mina Desai ◽

Zhice Xu ◽

Catalina Guerra ◽

Nathash Kallichanda ◽

Michael G. Ross

Keyword(s):

Amniotic Fluid ◽

Tap Water ◽

Plasma Osmolality ◽

Cardiovascular Responses ◽

Urine Flow ◽

Fluid Volume ◽

Plasma Sodium ◽

Amniotic Fluid Volume ◽

Fetal Urine ◽

The Impact

Maternal administration of DDAVP induces maternal and fetal plasma hyponatremia, accentuates fetal urine flow, and increases amniotic fluid volume. Fetal hemorrhage represents an acute stress that results in fetal AVP secretion and reduced urine flow rate. In view of the potential therapeutic use of DDAVP for pregnancies with reduced amniotic fluid volume, we sought to examine the impact of maternal hypotonicity during acute fetal hemorrhage. Chronically catheterized pregnant ewes (130 ± 2 days) were allocated to control or to DDAVP-induced hyponatremia groups. In the latter group, tap water (2,000 ml) was administered intragastrically to the ewe followed by DDAVP (20 μg bolus, 4 μg/h) and a maintenance intravenous infusion of 5% dextrose water for 4 h to achieve maternal hyponatremia of 10–12 meq/l. Thereafter, ovine fetuses from both groups were continuously hemorrhaged to 30% of estimated blood volume over a 60-min period. DDAVP caused similar degree of reductions in plasma sodium and osmolality in pregnant ewes and their fetuses. In response to hemorrhage, DDAVP fetuses showed greater reduction in hematocrit than control fetuses (14 vs. 10%). Both groups of fetuses demonstrated similar increases in plasma AVP concentration. However, the AVP-hemorrhage threshold was greater in DDAVP fetuses (22.5%) than in control (17.5%). Hemorrhage had no significant impact on plasma osmolality, electrolyte levels, or cardiovascular responses in either group of fetuses. Despite similar increases in plasma AVP, DDAVP fetuses preserved fetal urine flow rates, with values threefold those of control fetuses. These results suggest that under conditions of acute fetal stress of hemorrhage, maternal DDAVP may preserve fetal urine flow and amniotic fluid volume.

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Renal function in the chronically cannulated fetal llama: comparison with studies in the ovine fetus

Reproduction Fertility and Development ◽

10.1071/rd9951311 ◽

1995 ◽

Vol 7 (5) ◽

pp. 1311 ◽

Cited By ~ 3

Author(s):

EM Wintour ◽

R Riquelme ◽

C Gaete ◽

C Rabasa ◽

E Sanhueza ◽

...

Keyword(s):

Amniotic Fluid ◽

Flow Rate ◽

Urine Flow ◽

Urine Flow Rate ◽

Fetal Kidney ◽

Fetal Plasma ◽

Post Surgery ◽

Fetal Urine ◽

Ovine Fetus ◽

Ovine Fetal

Samples of maternal and fetal plasma, fetal urine, and amniotic fluid were collected from 8 chronically cannulated pregnant llamas, in the last third of gestation. The samples were obtained for up to 18 days post-surgery. Osmolality, sodium (Na), potassium (K), chloride (Cl), and urea were measured on 40 samples collected on days 1, 2, 3, 4-5, 6-7, 8-9, and 10-19. The osmolalities of maternal and fetal plasma, fetal urine and amniotic fluid, averaged over these 7 time periods, were, respectively, 312 +/- 2, 311 +/- 1, 484 +/- 14, and 317 +/- 1 mosmol kg-1. Values are given as mean +/- s.e. The major differences from fetal fluid values in the ovine fetus (from previously published values) were the higher osmolality and urea concentration of llama fetal urine. Urine flow rate measured in 6 fetuses, 4.5-6.5 kg body weight, was 5.8 +/- 0.4 mliter h-1; urea clearance rate was 55.5 +/- 11.8 mliter h-1. Glomerular filtration rate (GFR), measured with 51Cr-EDTA in 5 fetuses on 1-4 occasions, was 111.4 +/- 23.3 mliter h-1. Fractional reabsorptions (FR) of Na, K and Cl were 97.9 +/- 1, 75.9 +/- 13.5 and 97.7 +/- 0.4% respectively. The GFR (25 mliter kg-1 h-1) and urine flow rate (1 mL kg-1 h-1) were less than half and about one-tenth the respective values in ovine fetuses. As Na reabsorption is the major oxygen-consuming activity of the kidney, the llama fetal kidney requires only half the oxygen needed by the ovine fetal kidney to reabsorb the filtered sodium load. The reason for the formation of hypertonic, rather than hypotonic, urine in the fetal llama may be due to both greater morphological maturity of the kidney and the excretion of as yet unidentified osmotically active organic substances.

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DDAVP-induced maternal hyposmolality increases ovine fetal urine flow

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1995.268.2.r358 ◽

1995 ◽

Vol 268 (2) ◽

pp. R358-R365 ◽

Cited By ~ 3

Author(s):

M. J. Nijland ◽

M. G. Ross ◽

L. K. Kullama ◽

K. Bradley ◽

M. G. Ervin

Keyword(s):

Tap Water ◽

Control Period ◽

Plasma Osmolality ◽

Urine Osmolality ◽

Maternal Plasma ◽

Urine Flow ◽

Fetal Plasma ◽

Maternal Urine ◽

Fetal Urine ◽

Fluid Transfer

Fetal urine flow is influenced by fetal intravascular volume, glomerular filtration rate, tubular reabsorption, and fluid regulatory hormones. As maternal-to-fetal fluid transfer is dependent on hydrostatic and osmotic gradients, we postulated that a chronic decrease in maternal plasma osmolality would promote transplacental fluid transfer and increase fetal urine flow. Six pregnant ewes and singleton fetuses (131 +/- 2 days; term = 150 days) received bladder and hindlimb arterial and venous catheters. After 5 days, plasma and urine composition, urine flow rate (Uvol), and plasma arginine vasopressin (AVP) levels were measured during a 2-h control period. At 2 h, tap water (2 liter, 38 degrees C) was administered to the ewe. At 3 h, ewes received a 20-micrograms bolus of 1-desamino-[D-Arg8]vasopressin (DDAVP), followed by continuous infusion (4 micrograms/h). In response to water loading, maternal urine osmolality decreased (761 +/- 158 to 339 +/- 13 mosmol/kgH2O), and Uvol increased. After DDAVP, maternal urine osmolality increased (1,270 +/- 89 mosmol/kgH2O), and Uvol, hematocrit, plasma osmolality (304 +/- 1 to 284 +/- 4 mosmol/kgH2O), and protein concentration decreased. Five hours after maternal DDAVP infusion, fetal plasma osmolality decreased (300 +/- 1 to 281 +/- 3 mosmol/kgH2O), and Uvol increased (0.4 +/- 0.1 to 1.3 +/- 0.2 ml/min) and remained elevated at 24 h. There was no change in fetal plasma DDAVP (immunoreactive AVP) levels or fetal urine osmolality. Controlled changes in maternal plasma osmolality may prove useful in modulating fetal urine flow and, ultimately, amniotic fluid volume.

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Ovine fetal swallowing and renal responses to oligohydramnios

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1994.266.3.r972 ◽

1994 ◽

Vol 266 (3) ◽

pp. R972-R978 ◽

Cited By ~ 8

Author(s):

L. K. Kullama ◽

C. L. Agnew ◽

L. Day ◽

M. G. Ervin ◽

M. G. Ross

Keyword(s):

Amniotic Fluid ◽

Volume Regulation ◽

Urine Osmolality ◽

Urine Flow ◽

Fetal Urine ◽

Chloride Excretion ◽

Fluid Production ◽

Ovine Fetus ◽

Ovine Fetal ◽

Renal Responses

Amniotic fluid (AF) volume regulation is dependent on a balance between fluid production and fluid resorption. We examined the effects of reduced AF volume on AF production by fetal urine and resorption by fetal swallowing and the response of these parameters to AF volume replacement. Eight time-dated pregnant ewes (125 +/- 1 days gestation) were studied before (day 1) and after (day 3) AF and fetal urine drainage. Drainage resulted in a significant decrease in AF volume (415 +/- 89 to 157 +/- 36 ml). Fetal urine osmolality increased (139 +/- 10 to 286 +/- 33 mosmol/kgH2O), while urine flow did not change significantly (0.31 +/- 0.04 to 0.23 +/- 0.06 ml/min), resulting in nonsignificant increases in osmolar, sodium, and chloride excretions. Fetal electromyographic swallowing activity decreased 30% (1.0 +/- 0.1 to 0.7 +/- 0.1 swallows/min; P < 0.05), while net esophageal flow decreased 74% (0.31 +/- 0.12 to 0.07 +/- 0.04 ml/min; P < 0.05). On day 4, 0.15 M NaCl (500 ml; 37 degrees C) was administered into the AF over 30 min. During the 2 h after reinfusion, urine flow (0.29 +/- 0.07 to 0.40 +/- 0.09 ml/min) and osmolar sodium and chloride excretion significantly increased, though fetal swallowing activity and esophageal flow did not change. Thus the ovine fetus responded to reduced AF volume by maintaining AF production and decreasing AF resorption. In response to AF replacement, urine flow increased while fetal swallowing activity did not change, consistent with an intramembranous pathway for fetal AF resorption.

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Fetal renal contribution to amniotic fluid osmolality during maternal hypertonicity

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1986.250.2.r235 ◽

1986 ◽

Vol 250 (2) ◽

pp. R235-R239

Author(s):

L. L. Woods

Keyword(s):

Amniotic Fluid ◽

Continuous Infusion ◽

Arginine Vasopressin ◽

Urine Osmolality ◽

Uterine Wall ◽

Urine Flow ◽

Bulk Flow ◽

Vasopressin Antagonist ◽

Fetal Plasma ◽

Fetal Urine

The contribution of fetal urine to the increase in amniotic fluid osmolality during maternal hypertonicity was studied in chronically catheterized sheep of 130-135 days gestation. Nine percent NaCl was injected simultaneously into fetal and maternal veins, followed by a continuous infusion into the maternal vein. Maternal and fetal plasma osmolalities rose by 15 +/- 1 (SE) and 13 +/- 1 mosmol/kg, respectively, and remained constant for 4 h. Fetal urine osmolality rose significantly from 188 +/- 31 to 277 +/- 32 mosmol/kg within 1 h and remained constant thereafter. Fetal urine flow rose transiently, fell to normal within 10 min, and averaged 70% of normal beyond 1 h. Amniotic fluid osmolality rose by 10.8 +/- 2.8 mosmol/kg over 4 h. Following hypertonic injection into three fetuses blocked by the arginine vasopressin antagonist d(CH2)5D-tyr(Et)VAVP, urine osmolality did not change, and amniotic fluid osmolality rose by 2.7 +/- 0.3 mosmol/kg. Thus it appears that the increase in amniotic fluid osmolality during maternal hypertonicity may be due largely to an increased fetal urine osmolality coupled with a decreased flow of fetal urine into the amniotic space, rather than to bulk flow of fluid across the membranes and uterine wall.

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Effect of maternal glucocorticoid treatment on fetal fluids in sheep at 0.4 gestation

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1994.266.4.r1174 ◽

1994 ◽

Vol 266 (4) ◽

pp. R1174-R1181 ◽

Cited By ~ 2

Author(s):

E. M. Wintour ◽

D. Alcorn ◽

A. McFarlane ◽

K. Moritz ◽

S. J. Potocnik ◽

...

Keyword(s):

Amniotic Fluid ◽

Flow Rate ◽

Allantoic Fluid ◽

Urine Flow ◽

Fluid Volume ◽

Fluid Composition ◽

Glucocorticoid Treatment ◽

Amniotic Fluid Volume ◽

Fetal Urine ◽

Fetal Fluids

Treatment of nine pregnant Merino ewes (64.0 +/- 0.4 days of gestation) with dexamethasone (D; 0.76 mg/h for 48 h) resulted in significant alterations in fetal fluids compared with eight saline-infused control animals (S; 63.0 +/- 0.9 days). There was a substantial increase in allantoic fluid volume (177 +/- 18 ml, D vs. 31 +/- 6, S) but no change in amniotic fluid volume (248 +/- 12 ml, D; 305 +/- 24, S). For allantoic fluid there was a significant decrease in osmolality (213 +/- 4 mosmol/kg water, D; 230 +/- 5, S) and alterations in composition. Amniotic fluid osmolality was unchanged (292 +/- 2 mosmol/kg water, D; 293 +/- 1, S), but amniotic fluid composition was affected. In four fetuses in which bladder and amniotic cannulas were inserted at gestational age 68-75 days, fetal urine flow rate increased from a mean of 4.1 +/- 1.1 to 13.8 +/- 2.6 ml/h after 24 h and 11.8 +/- 3.0 ml/h at 48 h for a similar maternal D infusion, whereas no such increase occurred in four control fetuses. All the fetal urine voided during a 3.5- to 4-h infusion of 51Cr-labeled EDTA into the fetal bladder was directed to the allantois. The results suggest that the increase in allantoic fluid volume resulted from increased fetal urine output into the allantoic compartment, although the composition of the excess allantoic fluid differed substantially from that of fetal urine. There was a greater incidence of abnormal cotyledons in the D-infused ewes.(ABSTRACT TRUNCATED AT 250 WORDS)

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Function curve of the membranes that regulate amniotic fluid volume in sheep

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01284.2004 ◽

2005 ◽

Vol 289 (1) ◽

pp. H146-H150 ◽

Cited By ~ 12

Author(s):

Job Faber ◽

Debra Anderson ◽

Roger Hohimer ◽

Qin Yang ◽

George Giraud ◽

...

Keyword(s):

Amniotic Fluid ◽

Absorption Rate ◽

Plasma Renin ◽

Fluid Volume ◽

Natural Rate ◽

Fetal Plasma ◽

Amniotic Fluid Volume ◽

Urine Production ◽

Rate Of Absorption ◽

Vascular Catheters

Seven singleton 120-day fetal lambs were prepared with a shunt from the lung to the gastric end of the esophagus, a bladder catheter, and multiple amniotic fluid and vascular catheters. The urachus was ligated. Beginning 7 days later, amniotic fluid volumes were determined by drainage, followed by replacement with 1 liter of lactated Ringer (LR) solution. Urine flow into the amnion was measured continuously. In 14 of 27 experiments, amniotic fluid volumes were determined again 2 days after the inflow into the amnion had consisted of urine only and in 13 experiments after the inflow of urine had been supplemented by an intraamniotic infusion of LR solution. Intramembranous absorption was calculated from the inflows and the changes in volume between the beginning and end of each experiment. The relations between absorption rate and amniotic fluid volume, the “function curves,” were highly individual. Urine production during the infusion of LR solution did not decrease, fetal plasma renin activity decreased ( P < 0.001), and amniotic fluid volume increased by 140% [SE (27%), P < 0.005], but the increase in the amniochorionic absorption rate of 411% [SE (48%), P < 0.001] was greater ( P < 0.005) than the increase in volume. Each of the seven fetuses was proven capable of an average intramembranous absorption rate that exceeded 4.5 liters of amniotic fluid per day. During the infusion of LR solution, the increase in the rate of absorption matched the rate of infusion (both in ml/h), with a regression coefficient of 0.75 ( P < 0.001). Thus, even for large amniotic fluid volumes, volume is not limited by the absorptive capacity of the amniochorion, and, at least in these preparations, the position of the function curve and not the natural rate of inflow was the major determinant of resting amniotic fluid volume.

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Intraruminal rehydration of ovine fetuses

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1991.261.6.r1381 ◽

1991 ◽

Vol 261 (6) ◽

pp. R1381-R1387

Author(s):

M. G. Ross ◽

D. J. Sherman ◽

M. G. Ervin ◽

L. Day

Keyword(s):

Blood Pressure ◽

Glomerular Filtration Rate ◽

Filtration Rate ◽

Plasma Osmolality ◽

Urine Osmolality ◽

Distilled Water ◽

Intravascular Volume ◽

Fetal Plasma ◽

Arterial Blood ◽

Arterial Po2

During oral rehydration of adult mammals, oropharyngeal stimulation, the act of swallowing, and/or gastric factors contribute to a rapid decrease in plasma arginine vasopressin (AVP) that precedes plasma osmolality changes. To determine whether similar mechanisms are present in the developing fetus, six chronically prepared ovine fetuses were rehydrated with intraruminal (IR) distilled water infusions (1 ml.kg-1.min-1 for 60 min) after 43 +/- 3 h of maternal water deprivation. In response to maternal dehydration, significant increases were noted in maternal and fetal mean plasma osmolalities, sodium and AVP concentrations, and fetal urine osmolality. As estimated by hematocrit, fetal intravascular volume decreased by 11%. Fetal rehydration via IR distilled water infusion evoked a significant decrease in fetal plasma osmolality but no change in urine osmolality. Unexpectedly, fetal arterial blood pressure increased and arterial PO2 decreased while fetal hematocrit indicated a further 7% decrease in intravascular volume after the IR infusion. There was a nonsignificant trend toward increased fetal glomerular filtration rate, urine volume, and plasma AVP concentrations. Identical IR water infusions to five euhydrated fetuses resulted in significant decreases in fetal plasma osmolality and increases in glomerular filtration rate, urine flow, and osmolar excretion. The euhydrated fetuses also exhibited significant increases in mean arterial blood pressure and hematocrit and decreased fetal arterial PO2. These results indicate that IR water does not suppress AVP secretion in the dehydrated ovine fetus. Rather, both euhydrated and dehydrated fetuses exhibit an idiosyncratic vasoconstrictive response to IR water.

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